1. Field of the Invention
This invention relates to improved means for constraining a rumen drug delivery devices in a rolled configuration. More particularly, it relates to laminates comprising a water permeable material having a low friction surface in the presence of water, said material being bonded to a repulpable tape having a water-dispersible adhesive on both surfaces; to laminates comprising a flexible, water-permeable polymeric material bonded between the low friction surface material and the repulpable tape; and to devices so constrained.
2. Description of Related Art
Rumen drug delivery devices constrained in a rolled-up configuration by appropriate constraining means are disclosed in U.S. Pat. Nos. 4,228,149 and 4,601,893, the disclosures of which are incorporated herein by reference. U.S. Pat. No. 4,228,149 discloses sheets of drug-containing ethylene vinyl acetate copolymer, which may be coated on both surfaces by a water soluble polymer film, constrained in a rolled-up configuration. U.S. Pat. No. 4,601,893 teaches laminate devices comprising a drug-containing ethylene vinyl acetate copolymer sheet sandwiched between two coextensive films of ethylene vinyl acetate copolymer and having one or more macroperforations extending through all laminae, said laminae being constrained in a rolled-up configuration. U.S. application Ser. No. 170,495, filed Mar. 21, 1988, now abandoned, describes improved delivery devices of the type disclosed in U.S. Pat. No. 4,601,893. The improved devices are identical to those of U.S. Pat. No. 4,601,893 in construction but, in order to enhance their unrolling in the use environment, have been subjected to an annealing process prior to being constrained in a rolled configuration. The annealing process is conducted at a temperature of from about 40.degree. C. to about 80.degree. C., a range of about 43.degree. to 60.degree. C. being preferred. The time of annealing varies with the temperature of annealing. Further, the time and temperature vary with the manner in which the devices being annealed are arranged for the annealing step. The U.S. Pat. No. 4,601,893 type devices can be punched or cut to their approximate or actual size prior to annealing or the sheets from which the individual devices are punched can be annealed prior to punching out individual devices. The individual devices or sheets can be annealed individually or they can be stacked one upon the other to a height determined only by the size of the annealing equipment. The sheets can also be rolled for ease of handling prior to annealing and punching. In any case, stacking of the devices or sheets or rolling of the sheets generally requires temperatures toward the lower end of the indicated range and times toward the upper end of the range. Each arrangement requires determination of the conditions for optimum annealing. Temperatures which are too high may cause sticking of stacked devices, sheets or rolled sheets. Lower temperatures and longer times are best suited for stacked or rolled materials. For example, a roll of sheet material comprising a core 0.075 inches (1.91 mm) thick and outer layers each 0.05 inch (1.27 mm) thick, rolled on a 14 inch (35.56 cm) spindle to an overall diameter of 94 inches (238.76 cm), is desirably annealed for up to 96 hours at 43.degree. C. Thus, considering the parameters of temperature and overall thickness of the material to be annealed from about 96 to 4 hours is practical.
A further modification of the delivery devices of U.S. Pat. No. 4,601,893 is described in U.S. application Ser. No. 170,529, filed Mar. 21, 1988, now abandoned. Said modification comprises U.S. Pat. No. 4,601,893 type devices which have been coated on one side with an elastomer prior to being constrained in a rolled configuration. The elastomer coated side becomes the outer side of the device when the device is placed in a rolled configuration. The elastomer coated side improves the elasticity of the devices such that they recover or unroll from their constrained configuration to a greater extent and at a faster rate. The term "elastomer" as used herein is intended to embrace materials that, when stretched, snap back to their original or near-original shape. More specifically, it embraces thermoset and thermoplastic elastomers or elastoplastics, representative of which are styrene-diene block copolymers, polyurethanes, nitrile rubbers, olefinics and copolyester ethers, and preferably silicon rubbers (e.g. polydimethylsiloxanes). In each of said patents and applications the constraining means comprises a biodegradable material such as gelatin string or tape, water soluble adhesive or paper.
Within the use environment; i.e., the rumen, the constraining means is dissolved, destroyed, ruptured or otherwise removed to allow the rolled-up device to revert to its original, or near-original sheet configuration to prevent its expulsion from the rumen.
It has been observed that the prior art devices described above are sometimes expelled by the ruminant because of untimely removal of the constraining means within the rumen. Additionally, difficulty is often encountered upon oral administration of the constrained devices to young ruminants. Premature removal of the constraining means and subsequent unrolling of the constrained device or slow transit of the constrained device can lead to dosing problems. Thus, the need for improved constraining means for rumen drug delivery devices which will facilitate dosing of ruminants therewith and enable timely change of configuration in the rumen and eliminate expulsion of the device by the ruminant.